Pain inhibition is produced by stimulation of the midbrain periaqueductal gray (PAG) and lateral reticular formation (LRF), diencephalic periventricular gray (PVG), medial basal forebrain (MBF) and lateral hypothalamus (LH). Inhibition of nocisponsive dorsal horn neurons produced by stimulating PAG, PVG, LH, and MFB (but not LRF) is reduced by systemically-administered serotonin (5-HT) depletors/blockers, indicating involvement of 5-HT neurotransmission in these pain-suppressive effects. Inhibition produced by PAG, LRF, PVG, and LH stimulation is not blocked by the specific opiate antagonist naloxone, implying that non-opiate pathways underlie these effects. This project will investigate behavioral, neurochemical, neuroanatomical, and neurophysiological aspects of analgesia producted by focal electrical stimulation of these 5 brain sites. Some of the specific goals subsumed under this project include: (1) To thoroughly investigate the behavioral effects of stimulation of these brain areas. This includes determining the (a) specificity of stimulation-induced inhibition, (b) types of pain stimuli suppressed (c) effects of stimulation on the threshold and slope of behavioral stimulus-response functions. (2) To precisely describe the neurocircuitry involved by (a) examining the afferent and efferent projections of these brain sites (b) examining the potential involvement of the spinal cord dorsolateral funiculus, medullary n. raphe magnus and medullary n. reticularis paragigantocellularis in analgesia elicited from various brain sites. (3) To elucidate the role of supraspinal and spinal 5-HT and norepinephrine in analgesia elicited from various brain sites. (4) To be able to suggest new and practical treatment procedures for difficult or intractable pain syndromes in man.